目的 制备紫草素脂质纳米粒（shikonin lipid nanoparticles，Shi-LNPs），进行相关表征及体外透皮性能研究。方法 采用高速搅拌超声法制备Shi-LNPs，通过静电吸附法对其进行壳聚糖修饰，得到壳聚糖修饰的紫草素脂质纳米粒（chitosan-modified shikonin lipid nanoparticles，CS@Shi-LNPs）。通过外观与形貌观察、粒径、多分散指数（polydispersity index，PDI）、ζ电位测定、差示扫描量热法（differential scanning calorimetry，DSC）以及X射线衍射（X-ray diffraction，XRD）研究等表征手段，对所得制剂进行质量评价；采用动态透析法与仿生膜法2种方法考察CS@Shi-LNPs的体外释药行为；其次，采用Franz扩散池法考察CS@Shi-LNPs的经皮渗透能力及真皮滞留性能。结果 CS@Shi-LNPs包封率为（99.22±0.09）%，载药量为（1.65±0.12）%。该纳米粒为均一液体，具有丁达尔效应，在透射电子显微镜（transmission electron microscope，TEM）下外形圆整、分散均匀，平均粒径为（184.7±4.6）nm，PDI为0.255±0.023，壳聚糖修饰前平均ζ电位为（−33.15±0.59）mV，修饰后平均ζ电位为（5.22±0.08）mV，为正电荷，表明壳聚糖成功修饰到Shi-LNPs颗粒上。DSC与XRD结果表明，紫草素被包裹于脂质中形成LNPs，呈无定形状态，CS@Shi-LNPs成功制备。体外释药实验显示，CS@Shi-LNPs具备缓控释释药特性，考察其30 h累积释放率，结果2种方法的累积释放率分别为（62.39±9.08）%和（56.92±1.97）%，体外透皮实验表明，CS@Shi-LNPs中紫草素在30 h内累积渗透量为（14.27±1.58）μg/cm²，相比Shi-LNPs均有所提高。结论 Shi-LNPs处方工艺合理，具有良好的透皮性能和真皮滞留性能。

Objective To prepare the lipid nanoparticles of shikonin (Shi-LNPs) and study its charaterization and the osmotic dynamics of in vitro skin. Methods Shikonin lipid nanoparticles were prepared by high-speed stirring sonication and modified with chitosan (CS) by electrostatic adsorption to obtain CS@Shi-LNPs. Characterization tools including appearance and morphology, particle size, polydispersity index (PDI), ζ potential measurement, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies were used to evaluate the quality of the resulting formulations. Dynamic dialysis and biomimetic membrane were used to investigate the in vitro drug release behavior of CS@Shi-LNPs. The Franz diffusion pool method was used to investigate the transdermal permeability and dermal retention properties of CS@Shi-LNPs. Results The CS@Shi-LNPs encapsulation rate was of (99.22 ±0.09)% and drug loading of (1.65 ±0.12)%. The nanoparticles are homogeneous liquid with Tyndall effect, rounded shape and uniform dispersion under transmission electron microscope (TEM), with an average particle size of (184.7 ±4.6) nm and PDI of 0.255 ±0.023. The average ζ potential was (−33.15 ±0.59) mV before chitosan modification, and the average ζ potential was positively charged to (5.22 ±0.08) mV after modification, indicating successful modification of chitosan onto Shi-LNPs particles. DSC and XRD results showed that shikonin was encapsulated in the lipid to form LNPs in an amorphous state. CS@Shi-LNPs was successfully prepared. The in vitro drug release experiments showed that CS@Shi-LNPs possessed the characteristics of slow and controlled release, with the cumulative release rates of (62.39 ±9.08)% and (56.92 ±1.97)% for 30 h, respectively. The in vitro permeation experiments showed that the cumulative permeation amount of shikonin in CS@Shi-LNPs at 30 h was (14.27 ±1.58) μg/cm², both of which were increased compared to Shi-LNPs. Conclusion The Shi-LNPs prescription process is reasonable and has good transdermal properties and dermal retention properties.

R283.6

国家自然科学基金资助项目（82173982）;广东省自然科学基金资助项目（2022A1515011382）